Platelets, or thrombocytes, are the constituents of whole blood that form platelet plugs that seal damaged blood vessels and also participate in the mechanisms leading to the formation of blood clots.
People with certain diseases like thrombocytopenia, leukemia, and other cancers, either as a consequence of the disease itself, or of the chemotherapy to treat the cancer, have a reduced number of platelets in their bloodstreams, and without adequate platelets, they bleed abnormally and bruise easily. Regular platelet transfusions are thus essential treatment for these and other patients.
Platelets must be obtained from whole blood donations, typically by separation of the whole blood components via gravitational force in a centrifuge. The force of the centrifuge causes the whole blood to separate based on cell density. The upper layer captured in the centrifuge is plasma. The middle layer is the buffy coat. The bottom, heaviest layer is packed red blood cells. The majority of platelets collected in this way are found in the buffy coat layer. To extract as many platelets as possible, buffy coats are pooled from several donations and re-spun in a centrifuge to separate the platelets from the rest of the buffy coat.
The platelet concentrates are suspended in a liquid, such as plasma. However, while effective as a platelet storage medium, plasma is a valuable blood component that can be used or further processed to purify proteins for use for the treatment of patients with other disorders.
Platelet additive solutions (PAS) have been under development for decades as an alternate platelet suspension and storage medium (for review see Ringwald et al., Transfusion Medicine Reviews 20(2):158-164, 2006a), and apart from making more plasma available for other purposes, they have certain notable advantages. In particular, the use of PASs has been shown to support platelet storage, reduce allergic and febrile transfusion reactions, facilitate ABO-incompatible platelet transfusions, and has more recently been used in conjunction with certain pathogen inactivation methods.
A number of PASs have been described, such as those disclosed in U.S. Pat. No. 6,613,566 (Kandler et al.), and by van der Meer et al. (Transfusion Medicine 11:193, 2001), Gullikson (Transfusion Medicine 10:257-264, 2000), Ringwald et al., 2005 (Vox Sanguinis 89:11-18, 2005), Ringwald et al., 2006b (Transfusion 46:236, 2006) and Ringwald et al. 2006a (supra). PASs are generally known to comprise sodium chloride, sodium citrate and sodium acetate. Alternative PAS have also included phosphate, potassium and magnesium.
Using the currently known PAS formulations, platelet production from centrifuged pooled buffy-coats by semi-automated blood component extractors is difficult. The necessary low speed centrifugation used to pellet red cells but leave the platelets in the supernatant results in an inherently unstable interface. In a production environment, the required ultra-gentle handling of blood bags with such unstable interfaces slows down blood component production, decreases platelet recoveries, and necessitates repeated centrifugations that jeopardize blood bag integrity.
Since such delicate care must be used, blood component production with known PASs is typically slower than with plasma, with significant economic implications. This makes many blood centers reluctant to utilize is PASs despite their noted advantages.
Surprisingly, the present inventors have observed that the difficulty in working with the traditional PAS formulations can be ameliorated through the addition of a viscous component to the PAS.